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While transcriptional regulation has been well characterized, post\u2010transcriptional RNA processing has recently emerged as a crucial determinant of cardiac homeostasis. This review summarizes current knowledge of RNA modifications, alternative splicing, mRNA stability, and RNA editing in physiological and pathological hypertrophy. We highlight key epitranscriptomic marks such as N6\u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A), 5\u2010methylcytosine (m\n                    <jats:sup>5<\/jats:sup>\n                    C), and 7\u2010methylguanosine (m\n                    <jats:sup>7<\/jats:sup>\n                    G), as well as the functions of RNA\u2010binding proteins and adenosine deaminases acting on RNA (ADAR1\/2). In exercise\u2010induced hypertrophy, RNA processing contributes to adaptive remodeling by supporting sarcomere organization, calcium handling, and survival pathways, exemplified by RBFOX2\u2010dependent splicing of CACNA1C, RBM20\u2010directed regulation of titin isoforms, and METTL14\u2010mediated m\n                    <jats:sup>6<\/jats:sup>\n                    A signaling that enhances Akt activity. Conversely, pathological stress leads to dysregulated RNA programs that promote maladaptive remodeling through aberrant splice variants, perturbation of circular RNAs, and persistent pro\u2010inflammatory signaling, thereby facilitating contractile dysfunction and progression to heart failure. Context\u2010dependent regulators, including METTL3, YTHDF2, RBM24, and ADAR2, orchestrate the balance between adaptive and maladaptive responses. Targeting specific nodes, such as METTL3\u2010driven m\n                    <jats:sup>6<\/jats:sup>\n                    A methylation or RBM24\u2010dependent splicing fidelity, may provide innovative therapeutic strategies. Advances in RNA\u2010targeted interventions, including ADAR\u2010mediated editing and small molecule inhibitors of methyltransferases, highlight the translational potential of RNA processing as a novel avenue for precision cardiovascular therapy.\n                  <\/jats:p>","DOI":"10.1096\/fj.202503525r","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T11:37:07Z","timestamp":1769686627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RNA Processing in Cardiac Hypertrophy: Coordinating Physiological Adaptation and Pathological Remodeling"],"prefix":"10.1096","volume":"40","author":[{"given":"Mengling","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Cardiology The First Hospital of Jilin University  Changchun 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